CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-024014
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 NF-kappa-B essential modulator 
Protein Synonyms/Alias
 NEMO; FIP-3; IkB kinase-associated protein 1; IKKAP1; Inhibitor of nuclear factor kappa-B kinase subunit gamma; I-kappa-B kinase subunit gamma; IKK-gamma; IKKG; IkB kinase subunit gamma; NF-kappa-B essential modifier 
Gene Name
 IKBKG 
Gene Synonyms/Alias
 FIP3; NEMO 
Created Date
 July 27, 2013 
Organism
 Homo sapiens (Human) 
NCBI Taxa ID
 9606 
Lysine Modification
Position
Peptide
Type
References
179VERLGLEKLDLKRQKubiquitination[1, 2]
233SRLEAATKECQALEGubiquitination[2]
323SVVGSERKRGMQLEDubiquitination[2]
353QEVIDKLKEEAEQHKubiquitination[2]
377KAQADIYKADFQAERubiquitination[2, 3]
Reference
 [1] Systems-wide analysis of ubiquitylation dynamics reveals a key role for PAF15 ubiquitylation in DNA-damage bypass.
 Povlsen LK, Beli P, Wagner SA, Poulsen SL, Sylvestersen KB, Poulsen JW, Nielsen ML, Bekker-Jensen S, Mailand N, Choudhary C.
 Nat Cell Biol. 2012 Oct;14(10):1089-98. [PMID: 23000965]
 [2] Refined preparation and use of anti-diglycine remnant (K-ε-GG) antibody enables routine quantification of 10,000s of ubiquitination sites in single proteomics experiments.
 Udeshi ND, Svinkina T, Mertins P, Kuhn E, Mani DR, Qiao JW, Carr SA.
 Mol Cell Proteomics. 2013 Mar;12(3):825-31. [PMID: 23266961]
 [3] hCKSAAP_UbSite: improved prediction of human ubiquitination sites by exploiting amino acid pattern and properties.
 Chen Z, Zhou Y, Song J, Zhang Z.
 Biochim Biophys Acta. 2013 Aug;1834(8):1461-7. [PMID: 23603789] 
Functional Description
 Regulatory subunit of the IKK core complex which phosphorylates inhibitors of NF-kappa-B thus leading to the dissociation of the inhibitor/NF-kappa-B complex and ultimately the degradation of the inhibitor. Its binding to scaffolding polyubiquitin seems to play a role in IKK activation by multiple signaling receptor pathways. However, the specific type of polyubiquitin recognized upon cell stimulation (either 'Lys-63'- linked or linear polyubiquitin) and its functional importance is reported conflictingly. Also considered to be a mediator for TAX activation of NF-kappa-B. Could be implicated in NF-kappa-B- mediated protection from cytokine toxicity (By similarity). Essential for viral activation of IRF3. Involved in TLR3- and IFIH1-mediated antiviral innate response; this function requires 'Lys-27'-linked polyubiquitination. 
Sequence Annotation
 ZN_FING 396 417 C2HC-type.
 REGION 44 111 Interaction with CHUK/IKBKB.
 REGION 150 257 Interaction with TANK.
 REGION 242 350 Ubiquitin-binding (UBD).
 REGION 246 365 Self-association.
 REGION 251 419 Required for interaction with TNFAIP3.
 REGION 322 343 Leucine-zipper (Potential).
 REGION 382 419 Interaction with CYLD.
 MOD_RES 31 31 Phosphoserine; by IKKB.
 MOD_RES 43 43 Phosphoserine; by IKKB.
 MOD_RES 68 68 Phosphoserine.
 MOD_RES 85 85 Phosphoserine; by ATM.
 MOD_RES 376 376 Phosphoserine; by IKKB.
 DISULFID 54 54 Interchain.
 DISULFID 347 347 Interchain.
 CROSSLNK 111 111 Glycyl lysine isopeptide (Lys-Gly)
 CROSSLNK 139 139 Glycyl lysine isopeptide (Lys-Gly)
 CROSSLNK 143 143 Glycyl lysine isopeptide (Lys-Gly)
 CROSSLNK 226 226 Glycyl lysine isopeptide (Lys-Gly)
 CROSSLNK 246 246 Glycyl lysine isopeptide (Lys-Gly)
 CROSSLNK 264 264 Glycyl lysine isopeptide (Lys-Gly)
 CROSSLNK 277 277 Glycyl lysine isopeptide (Lys-Gly)
 CROSSLNK 277 277 Glycyl lysine isopeptide (Lys-Gly)
 CROSSLNK 283 283 Glycyl lysine isopeptide (Lys-Gly)
 CROSSLNK 285 285 Glycyl lysine isopeptide (Lys-Gly)
 CROSSLNK 292 292 Glycyl lysine isopeptide (Lys-Gly)
 CROSSLNK 302 302 Glycyl lysine isopeptide (Lys-Gly)
 CROSSLNK 309 309 Glycyl lysine isopeptide (Lys-Gly)
 CROSSLNK 309 309 Glycyl lysine isopeptide (Lys-Gly)
 CROSSLNK 321 321 Glycyl lysine isopeptide (Lys-Gly)
 CROSSLNK 325 325 Glycyl lysine isopeptide (Lys-Gly)
 CROSSLNK 326 326 Glycyl lysine isopeptide (Lys-Gly)
 CROSSLNK 399 399 Glycyl lysine isopeptide (Lys-Gly)  
Keyword
 3D-structure; Alternative splicing; Coiled coil; Complete proteome; Cytoplasm; Direct protein sequencing; Disease mutation; Disulfide bond; Ectodermal dysplasia; Host-virus interaction; Isopeptide bond; Metal-binding; Nucleus; Osteopetrosis; Phosphoprotein; Reference proteome; Transcription; Transcription regulation; Ubl conjugation; Zinc; Zinc-finger. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 419 AA 
Protein Sequence
MALVIQVGKL RPREVRTPQT INPSLFPSLP VKLSSIIEVP SGGERCCSRR TLVYKARAFW 60
KGAPLPCWMN RHLWKSQLCE MVQPSGGPAA DQDVLGEESP LGKPAMLHLP SEQGAPETLQ 120
RCLEENQELR DAIRQSNQIL RERCEELLHF QASQREEKEF LMCKFQEARK LVERLGLEKL 180
DLKRQKEQAL REVEHLKRCQ QQMAEDKASV KAQVTSLLGE LQESQSRLEA ATKECQALEG 240
RARAASEQAR QLESEREALQ QQHSVQVDQL RMQGQSVEAA LRMERQAASE EKRKLAQLQV 300
AYHQLFQEYD NHIKSSVVGS ERKRGMQLED LKQQLQQAEE ALVAKQEVID KLKEEAEQHK 360
IVMETVPVLK AQADIYKADF QAERQAREKL AEKKELLQEQ LEQLQREYSK LKASCQESAR 420
IEDMRKRHVE VSQAPLPPAP AYLSSPLALP SQRRSPPEEP PDFCCPKCQY QAPDMDTLQI 480
HVMECIE 487 
Gene Ontology
 GO:0008385; C:IkappaB kinase complex; TAS:UniProtKB.
 GO:0005634; C:nucleus; IDA:UniProtKB.
 GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
 GO:0004871; F:signal transducer activity; TAS:ProtInc.
 GO:0000187; P:activation of MAPK activity; TAS:Reactome.
 GO:0007250; P:activation of NF-kappaB-inducing kinase activity; IEA:Compara.
 GO:0001782; P:B cell homeostasis; IEA:Compara.
 GO:0007249; P:I-kappaB kinase/NF-kappaB cascade; TAS:UniProtKB.
 GO:0006917; P:induction of apoptosis; TAS:ProtInc.
 GO:0006954; P:inflammatory response; TAS:UniProtKB.
 GO:0045087; P:innate immune response; TAS:UniProtKB.
 GO:0007254; P:JNK cascade; TAS:Reactome.
 GO:0002755; P:MyD88-dependent toll-like receptor signaling pathway; TAS:Reactome.
 GO:0070423; P:nucleotide-binding oligomerization domain containing signaling pathway; TAS:Reactome.
 GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB cascade; TAS:Reactome.
 GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; IDA:UniProtKB.
 GO:0032481; P:positive regulation of type I interferon production; TAS:Reactome.
 GO:0006974; P:response to DNA damage stimulus; IDA:UniProtKB.
 GO:0009615; P:response to virus; TAS:UniProtKB.
 GO:0050852; P:T cell receptor signaling pathway; NAS:UniProtKB.
 GO:0034166; P:toll-like receptor 10 signaling pathway; TAS:Reactome.
 GO:0034134; P:toll-like receptor 2 signaling pathway; TAS:Reactome.
 GO:0034138; P:toll-like receptor 3 signaling pathway; TAS:Reactome.
 GO:0034142; P:toll-like receptor 4 signaling pathway; TAS:Reactome.
 GO:0034146; P:toll-like receptor 5 signaling pathway; TAS:Reactome.
 GO:0034162; P:toll-like receptor 9 signaling pathway; TAS:Reactome.
 GO:0038123; P:toll-like receptor TLR1:TLR2 signaling pathway; TAS:Reactome.
 GO:0038124; P:toll-like receptor TLR6:TLR2 signaling pathway; TAS:Reactome.
 GO:0006351; P:transcription, DNA-dependent; IEA:UniProtKB-KW.
 GO:0035666; P:TRIF-dependent toll-like receptor signaling pathway; TAS:Reactome.
 GO:0019048; P:virus-host interaction; IEA:UniProtKB-KW. 
Interpro
 IPR021063; NEMO_N. 
Pfam
 PF11577; NEMO 
SMART
  
PROSITE
  
PRINTS